The present invention is directed to novel compounds which are 1,2,4-oxadiazole and 1,2,4-thiadiazole derivatives of the fenamic acids (in which the fenamate residue is present at the 3-position of the 1,2,4-oxadiazole or 1,2,4-thiadiazole), and pharmaceutically acceptable acid addition or base salts thereof, pharmaceutical compositions, and methods of use thereof. The invention compounds are found to have activity as inhibitors of cyclooxygenase and/or 5-lipoxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and the like.
Fenamates have been previously described as antiinflammatory agents and, particularly, various oxadiazole and thiadiazoles as useful substituents in derivations thereof. For example, 1,3,4-oxadiazole and 1,3,4-thiadiazoles are described in copending United States application Ser. No. 07/769/562. Certain 1,2,4-oxadiazole and 1,2,4-thiadiazoles are also described together with 3,5-di-tertiary-butyl-4-hydroxyphenyl groups in European Patent Publication 371,438. Nevertheless, the present combination of ring systems, substituents, and moieties is not among those previously known.